Circ_0004491 stimulates guanine nucleotide-binding protein alpha subunit to inhibit the malignant progression of oral squamous cell carcinoma by sponging miR-2278

BACKGROUND/PURPOSE: Circular RNA origin recognition complex subunit 4 (circORC4; ID: hsa_circ_0004491) have been confirmed to be a novel potential biomarker of oral squamous cell carcinoma (OSCC). This study aimed to explore the molecular mechanism of circ_0004491 in OSCC progression. MATERIALS AND METHODS: Levels of circ_0004491, microRNA (miR)-2278, guanine nucleotide-binding protein alpha subunit (GNAS), Bax, Bcl-2, E-cadherin and ki-67 were detected by quantitative real-time PCR, western blotting and immunohistochemistry. The proliferation of OSCC cells was measured using colony formation assay and EdU staining. Cell apoptosis and motility were detected by flow cytometry and transwell assays respectively. Interaction between miR-2278 and circ_0004491 or GNAS was predicted by bioinformatics analysis and confirmed via luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model was used to analyze the role of circ_0004491 in tumor growth in vivo. RESULTS: Circ_0004491 was downregulated in OSCC tissues and cell lines. Circ_0004491 overexpression suppressed the proliferation, migration and invasion whereas facilitated the apoptosis of OSCC cells. Circ_0004491 acted as a molecular sponge for miR-2278, and circ_0004491 overexpression-mediated effect was partly reversed by miR-2278 mimic in OSCC cells. MiR-2278 interacted with the 3’UTR of GNAS. Circ_0004491 contributed to GNAS level by sponging miR-2278 in OSCC cells. GNAS knockdown restored miR-2278 inhibitor-mediated effect in OSCC cells. Circ_0004491 overexpression repressed xenograft tumor growth in vivo. CONCLUSION: Circ_0004491 can repress OSCC progression by regulation of miR-2278/GNAS axis, providing a possible circRNA-targeted therapy for OSCC.